DEXEDRINE®
SmithKline Beecham
Dextroamphetamine Sulfate
Sympathomimetic
Action And Clinical Pharmacology: Dextroamphetamine (dexamphetamine, d-amphetamine) sulfate is a sympathomimetic agent with indirect effects on adrenergic receptors. It has alpha-and beta-adrenergic activity. It has actions qualitatively similar to those of amphetamine sulfate but is approximately twice as potent. It has a marked stimulant effect on the CNS, particularly the cerebral cortex and the respiratory and vasomotor centers.
Dextroamphetamine sulfate causes a lessening of fatigue, an increase in mental activity, an elevation of mood, and a general feeling of well-being. However, its indiscriminate use in attempts to increase capacity for work or to overcome fatigue is undesirable. At high doses, it produces a euphoria, which upon abrupt withdrawal of the drug reverts to severe depression and lethargy.
The mechanism by which amphetamines produce mental and behavioral effects in children is not conclusively established.
Indications And Clinical Uses: In the adjunctive treatment of: narcolepsy.
Attention-Deficit Hyperactivity Disorder: Dextroamphetamine may be used as an integral component of a treatment program, typically in combination with psychological, educational, or social measures for a stabilizing effect in children exhibiting the following behavioral syndrome: moderate-to-severe distractibility, short attention span, hyperactivity, emotional lability, and impulsivity. A diagnosis should not be made for symptoms of comparatively recent origin. Nonlocalizing (soft) neurological signs, learning disability, and EEG abnormalities may or may not be present. A diagnosis of CNS dysfunction may be warranted in some, but not all, cases.
Drug treatment is not indicated for all children with Attention-Deficit Hyperactivity Disorder. Stimulants are not appropriate for the treatment of children who are exhibiting symptoms which are secondary to environmental factors and/or primary psychiatric disorders, including psychosis. Suitable educational placement and psychosocial intervention are important. The prescription of stimulant medication will depend upon the physician’s evaluation of the chronicity and severity of symptoms in a child whose disorder has proved refractory to remedial measures alone.
Contra-Indications: Advanced arteriosclerosis, symptomatic cardiovascular disease, moderate to severe hypertension, hyperthyroidism, hypersensitivity or idiosyncrasy to sympathomimetic amines, agitated states, history of drug abuse, glaucoma.
During administration or within 14 days following the withdrawal of MAO, administration of dextroamphetamine may cause hypertensive crises.
Manufacturers’ Warnings In Clinical States: Amphetamines have been subject to extensive abuse. Tolerance, extreme psychological dependence, and severe social disability can occur. Patients have been reported to increase their dosage to many times the recommended level. The smallest possible amount of the drug should be prescribed or dispensed at one time.
Precautions: Occupational Hazards: Amphetamines may mask extreme fatigue which can impair the ability to perform potentially hazardous activities such as operating machinery or driving motor vehicles; patients should be cautioned accordingly.
Use with caution even in mild hypertension.
Amphetamines may alter insulin requirements in diabetes mellitus, and may decrease the hypotensive effect of guanethidine.
Dextroamphetamine products contain tartrazine (FD&C yellow #5) which can cause allergic type reactions (including bronchial asthma) in susceptible individuals. Cross-sensitivity to salicylates and tartrazine is frequently seen.
The possibility of tolerance and psychological dependence, particularly with excessive use, should be kept in mind. Therefore, care should be used in the selection of candidates for dextroamphetamine therapy. Should psychological dependence occur, discontinue medication. Abrupt cessation following prolonged high dosage administration may result in extreme fatigue and mental depression. Changes have also been noted on the sleep EEG.
Manifestations of chronic intoxication with amphetamines include severe dermatoses, marked insomnia, irritability, hyperactivity, and personality changes. The most severe manifestation of chronic intoxication is psychosis, often clinically indistinguishable from schizophrenia.
Use in Children: Amphetamines are not recommended for use in Attention-Deficit Hyperactivity Disorder in children under 6 years of age.
Long-term effects of amphetamines in children have not been well established.
Chronic administration of amphetamines may be associated with growth inhibition; growth should be monitored during treatment.
Clinical experience suggests that in psychotic children, administration of amphetamines may exacerbate symptoms of behavior disturbance and thought disorder.
The presence of tics or Tourette’s syndrome should be ruled out before administering amphetamines to children.
Drug Interactions: Caution should be exercised when coprescribing amphetamines and other drugs since clinically significant interactions with a number of drugs have been reported. In some instances, potentiation of CNS and cardiac effects could be life threatening. Dosages should be closely monitored.
Known interactions with amphetamines are as follows: Synergistic Interactions : tricyclic antidepressants, MAO inhibitors, meperidine, norepinephrine, phenobarbital, phenytoin, propoxyphene, acetazolamide, thiazides, gastrointestinal and urinary alkalinizing agents.
Antagonistic Interactions : adrenergic blockers, antihistamines, antihypertensives, chlorpromazine, ethosuximide, guanethidine, haloperidol, lithium carbonate, methenamine, Veratrum alkaloids, gastrointestinal and urinary acidifying agents.
Pregnancy: Safe use in pregnancy has not been established. Infants born to mothers dependent on amphetamines have an increased risk of premature delivery and low birth weight. Also, these infants may experience symptoms of withdrawal as manifested by dysphoria, agitation and significant lassitude. Reproductive studies in mammals at high multiples of the human dose have suggested an embryotoxic and a teratogenic potential. Use of amphetamines by women who are or who may become pregnant, and especially those in the first trimester of pregnancy, requires that the potential benefit be weighed against the possible hazard to mother and child.
Lactation: Amphetamines are excreted in human milk. Mothers taking dextroamphetamine should be advised to refrain from nursing.
Laboratory Test Interactions : Amphetamines can elevate plasma corticosteroid levels, particularly in the evening, and may interfere with urinary steroid determinations.
Adverse Reactions: Cardiovascular: palpitations, tachycardia, elevation of blood pressure. There have been isolated reports of cardiomyopathy associated with chronic amphetamine use.
CNS: overstimulation, restlessness, dizziness, euphoria or dysphoria, dyskinesia, headache, insomnia, exacerbation of motor and phonic tics, Tourette’s syndrome, tremor; rarely, psychotic episodes at recommended doses.
Gastrointestinal: dryness of the mouth, unpleasant taste, loss of appetite, diarrhea, constipation. other gastrointestinal disturbances, anorexia and weight loss.
Allergic: Urticaria.
Other: Impotence, changes in libido.
Symptoms And Treatment Of Overdose: The toxic dose of amphetamine varies widely according to the degree of tolerance present. Blood levels are, therefore, of little value in assessing the severity of the overdose; this assessment must depend almost entirely on clinical signs.Symptoms: Dilated and reactive pupils, shallow rapid respiration, rhabdomyolysis, hyperpyrexia, fever, chills, sweating, hyperactive tendon reflexes. Other symptoms are:
Central effects may include restlessness, tremor, aggressiveness, anxiety, confusion, delirium, hallucinations, panic attacks and even suicidal or homicidal tendencies. The stimulant effect is usually followed by depression, lethargy, exhaustion.
Cardiovascular effects may include anginal pain, extrasystoles and other arrhythmias, flushing, headache, hypertension or hypotension, pallor, palpitations, tachycardia. Circulatory collapse and syncope may occur.
Gastrointestinal effects include nausea, vomiting, diarrhea, abdominal cramps.
Fatal poisoning is usually preceded by convulsions and coma.
Treatment: Treatment is essentially symptomatic and supportive. In addition to the usual measures (including emesis, gastric lavage, catharsis), sedatives should be given when indicated. Oral or parenteral barbiturates are generally used for this purpose. To provide a basal level of sedation, one or more doses of sodium amobarbital may be given by mouth or, if necessary, by i.m. injection. This may be repeated as often as necessary and in quantities sufficient to control the symptoms.
Sedation may also be accomplished with chlorpromazine: in children 1 mg/kg body weight i.m. and in adults 100 mg i.m., repeated at half-hourly intervals if necessary. If the amphetamine has been taken with a barbiturate, as is often the case, the chlorpromazine dosage should be halved.
Note: It has been stated that the effects of amphetamines are best treated with haloperidol (Med Lett 1983 Sep 16;25:87), a dopamine antagonist with minimal anticholinergic side effects. Haloperidol, however, possesses central antiemetic properties; it may prolong the hypnotic action of barbiturates and may potentiate the effects of alcohol and other CNS depressant drugs; it may lower the convulsion threshold.
In general, the hypertension which may result from massive overdose of dextroamphetamine does not require treatment. A gradual drop in blood pressure will usually result when sufficient sedation has been administered. Phentolamine may be used to decrease blood pressure and hyperthermia. In the presence of severe hypotension, the usual procedures employed for shock should be instituted.
Acidification of the urine enhances excretion. Experience with forced diuresis, hemodialysis, peritoneal dialysis or charcoal hemoperfusion is inadequate to permit recommendations in this regard.
Since much of the Spansule capsule medication is coated for gradual release, therapy directed at reversing the effects of the ingested drug and at supporting the patient should be continued for as long as overdosage symptoms remain. Saline cathartics are useful for hastening the evacuation of pellets that have not already released medication.
Dosage And Administration: Regardless of indication, amphetamines should be administered at the lowest effective dosage, and dosage should be individually adjusted. Time of administration should receive special attention – particularly with the Spansule capsule form – because of possible insomnia. Late evening medication should be avoided.
Narcolepsy: Daily dosage may range from 5 to 60 mg, depending on individual patient response.
Suggested initial dosage for patients aged 6 to 12: start with 5 mg daily; daily dosage may be raised in increments of 5 mg at weekly intervals until optimal response is obtained.
In patients 12 years of age and older: start with 10 mg daily; daily dosage may be raised in increments of 10 mg at weekly intervals until optimal response is obtained.
If bothersome adverse reactions appear (e.g., insomnia or anorexia), dosage should be reduced. Spansule capsules may be used for once-a-day dosage wherever appropriate. With tablets, give first dose on awakening; additional doses (1 or 2) at intervals of 4 to 6 hours.
Attention-Deficit Hyperactivity Disorder in Children: Daily dosage may range from 2.5 to 40 mg, although some older children may require more than 40 mg daily for optimal response. If bothersome adverse reactions appear (e.g., insomnia or anorexia), dosage should be reduced. Spansule capsules may be used for once-a-day dosage wherever appropriate. With tablets, give first dose on awakening; additional doses (1 or 2) at intervals of 4 to 6 hours.
Not recommended for this use in children under 6 years of age.
In children 6 years of age or older, start with 5 mg once or twice daily; daily dosage may be raised in increments of 5 mg at weekly intervals until optimal response is obtained. Only in rare cases will it be necessary to exceed a total of 40 mg/day.
Most children suffering from Attention-Deficit Hyperactivity Disorder require medication for several years, although once symptoms have been controlled, it may be possible to reduce dosage or to interrupt drug therapy during the summer months and at other times when the child is under less stress. During periods of interrupted drug therapy, behavioral symptoms should be assessed to determine whether their recurrence is sufficient to justify the resumption of treatment.
Availability And Storage: Spansules: 10 mg: Each brown-capped, natural colored body taper-end capsule, with 3 shades of orange pellets, monogrammed “3513” on the cap with “10 mg” and “SB” on the body in white ink, contains: dextroamphetamine sulfate 10 mg, so prepared that a therapeutic dose is released promptly and the remaining dose, delivered gradually and without interruption, sustains the effect for 10 to 12 hours. Nonmedicinal ingredients: acacia, calcium sulfate, cetylpyridinium chloride, FD&C Blue No. 1, FD&C Red No. 40, FD&C Yellow No. 5, FD&C Yellow No. 6, gelatin, glyceryl distearate, glyceryl monostearate, nonpareil seeds, sodium lauryl sulfate, starch and white wax. Energy: 3.72 kJ (0.88 kcal). Bottles of 100.
15 mg: Each brown-capped, natural colored body taper-end capsule, with 3 shades of orange pellets, monogrammed “3514” on the cap with “15 mg” and “SB” on the body in white ink, contains: amphetamine sulfate 15 mg, so prepared that a therapeutic dose is released promptly and the remaining dose, delivered gradually and without interruption, sustains the effect for 10 to 12 hours. Nonmedicinal ingredients: acacia, calcium sulfate, cetylpyridinium chloride, FD&C Blue No. 1, FD&C Red No. 40, FD&C Yellow No. 5, FD&C Yellow No. 6, gelatin, glyceryl distearate, glyceryl monostearate, nonpareil seeds, sodium lauryl sulfate, starch and white wax. Energy: 4.78 kJ (1.14 kcal). Bottles of 100.
Tablets: Each orange, round-cornered, equilaterally triangular shaped, scored, compressed tablet, engraved “SKF E19”, contains: dextroamphetamine sulfate 5 mg. Nonmedicinal ingredients: calcium sulfate, confectioners sugar, gelatin, lactose, FD&C Yellow No. 5, FD&C Yellow No. 6, starch, stearic acid and talc. Energy: 1.46 kJ (0.35 kcal). Bottles of 100. (Shown in Product Recognition Section)
DEXEDRINE® SmithKline Beecham Dextroamphetamine Sulfate Sympathomimetic
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